The modulation of long-term potentiation by delta-9-tetrahydrocannabinol in the rat hippocampus, in vitro.

The duration of long-term potentiation (LTP) of the CA1 evoked field potential in rat hippocampal slices was significantly modulated by pre-treatment of slices with delta-9-tetrahydrocannabinol (THC) added to the incubation media. The three THC doses tested: 10 picomolar (pM), 100 pM, and 1000 pM, resulted in a biphasic change in population spike amplitude, such that 10 pM resulted in an increase, while 100 and 1000 pM resulted in dose-related decreases as compared to the control treatment. Upon subsequent induction of LTP by tetanizing stimulation, the THC treatments resulted in significant changes in the duration but not magnitude of potentiation. The early component of potentiation, post-tetanic potentiation, or PTP, was not affected by the THC treatments. LTP was seen to decay in an exponential manner over the 121 mini post-tetanus monitoring period. For comparisons of LTP duration, therefore, the half-life (t1/2) of LTP was extrapolated from linear regression analysis. The t1/2 values were determined for each treatment group from the slopes of the linear regression analysis of the logarithmically transformed time course data. While the control group t1/2 was determined as 280 min, the t1/2 for the THC groups were: 350 min (10 pM); 91 min (100 pM); and 33 min (1000 pM) doses, respectively. In context with previous reports of the disruptive action of marihuana intoxication on learning and memory, these results suggest that one possible action of THC may be in modulating hippocampal electrophysiology and its role in short-term memory processes.